Our current studies have demonstrated that the human endometrium contains a progestin-dependent, pregnancy-associated endometrial protein or PAEP. Furthermore, the endometrial levels of PAEP are markedly increased during the secretory phase of menstrual cycle and during early pregnancy and such an increase is associated with increase in serum progesterone levels. These observations have prompted us to extend our present study with the following specific aims in mind. (1) To determine whether a relationship exists in cycling women between tissue levels of PAEP and serum progesterone and estradiol levels, (2) to determine levels of PAEP in amniotic fluid during normal and abnormal pregnancies, (3) to determine whether progesterone can stimulate the synthesis of PAEP in endometrium in organ culture, and if so, to determine steroid-specificity of the response, (4) to test whether PAEP or other decidual proteins influence proteases and synthesis of human chorionic gonadotropin which are implicated in the trophoblastic growth and invasion of maternal tissue, (5) to determine whether PAEP is associated with lymphocytes of pregnant or non-pregnant women and to study effects of soluble decidual proteins on stimulated lymphocytes, (6) to determine whether PAEP binds steroid hormones, and (7) to improve the sensitivity of the existing radioimmunoassay for PAEP. This study will be jointly undertaken by a Reproductive Biologist, Gynecologic Endocrinologist and an Immunologist, using multiple biochemical and immunologic techniques in all of which the investigators have considerable experience. The proposed study may provide a means to monitor the uterine response to endogenous and exogenous progestins, and clarify the role, if at all any, of decidual proteins in the control of trophoblastic invasion of maternal tissue, immunosuppression and binding of steroids in pregnancy. Finally, the study of the response of endometrium in organ culture to steroids in vitro may lead to the development of an in vitro model for predicting the response of normal, and perhaps cancerous endometrium, to progestin therapy in women.